Matsumura Y, Hori T, Kawamata S, Imura A, Uchiyama T
Department of Hematology and Oncology, Research Center for Acquired Immunodeficiency Syndrome, The Institute for Virus Research, Kyoto University, Japan.
J Immunol. 1999 Sep 15;163(6):3007-11.
We investigated the intracellular signaling events of OX40 ligand (gp34), a member of the TNF family. To elucidate the intracellular signaling via gp34, we prepared a model system in which a human gp34-transfected mouse epithelial cell line was stimulated with a recombinant soluble form of OX40. We demonstrated that OX40 binding resulted in increase in c-jun and c-fos mRNA levels in this transfectant by Northern blot analysis, which was blocked by the pretreatment with anti-gp34 Ab. The studies with various gp34 deletion mutants showed that the cytoplasmic portion including the amino acid sequence 16-21 (RPRFER) was required for the induction of c-jun and c-fos mRNA expression. Furthermore, OX40 binding induced c-jun mRNA expression also in HUVECs, which in our previous study have been shown to express gp34 and interact with activated T cells through the OX40/gp34 pathway. On the other hand, c-fos mRNA was detectable neither in unstimulated HUVECs nor in gp34-stimulated HUVECs. These results indicate that the OX40/gp34 system generates two-way signals and may elicit biological effects on vascular endothelial cells.
我们研究了肿瘤坏死因子（TNF）家族成员OX40配体（gp34）的细胞内信号转导事件。为阐明通过gp34的细胞内信号转导，我们构建了一个模型系统，即用重组可溶性形式的OX40刺激转染了人gp34的小鼠上皮细胞系。通过Northern印迹分析，我们证明在该转染细胞中，OX40结合导致c-jun和c-fos mRNA水平升高，而抗gp34抗体预处理可阻断这种升高。对各种gp34缺失突变体的研究表明，诱导c-jun和c-fos mRNA表达需要包含氨基酸序列16 - 21（RPRFER）的细胞质部分。此外，在人脐静脉内皮细胞（HUVECs）中，OX40结合也诱导了c-jun mRNA表达，在我们之前的研究中已表明HUVECs表达gp34并通过OX40/gp34途径与活化的T细胞相互作用。另一方面，在未刺激的HUVECs或gp34刺激的HUVECs中均未检测到c-fos mRNA。这些结果表明，OX40/gp34系统产生双向信号，并可能对血管内皮细胞产生生物学效应。
